She began her career behind the scenes at the King's Head Theatre in London before taking on work as an assistant director at theatre companies including Paines Plough and the Royal Shakespeare Company. Early in her career she directed a number of early productions under the umbrella of her company Classics On A Shoestring.

The Department of Theatre and Performance at the Victoria and Albert Museum invited Mitchell and Leo Warner of 59 Productions to conceive and produce a video installation exploring the nature of 'truth in performance'.[5] Taking as its inspiration 5 of the most influential European theatre directors of the last century, the project examines how each of the practitioners would direct the actress playing Ophelia in the famous 'mad' scenes in Shakespeare’s Hamlet. This multiscreen video installation, launched at the Chantiers Europe festival at the Theatre de la Ville in Paris on 4 June, and opened at the V&A on 12 July 2011.[6]

She has been described as "a director who polarises audiences like no other" and "the closest thing the British theatre has to an auteur".[8] In 2007, the artistic director of the NT accused the British press of affording Mitchell's productions "misogynistic reviews, where everything they say is predicated on her sex".[9]

Her productions have been described as "distinguished by the intensity of the emotions, the realism of the acting, and the creation of a very distinctive world"[10] and accused of "a willful disregard for classic texts",[2] but Mitchell suggests that "there's a signature in every director's work"[10] and that it is not her intent to work to a "strong personal signature".[8]

Mitchell's process involves long and intensive rehearsal periods[11] and use of the Stanislavsky method. She regularly involves psychiatry in looking at characters, and in 2004 directed a series of workshops on Stanislavsky and neuroscience at the NT studio.[12][13] Since her 2006 play Waves, she has also experimented with video projections in a number of productions.[2]